Targeting PPARalpha in Alzheimer's Disease

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Journal Name: Current Alzheimer Research

Volume 15 , Issue 4 , 2018

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Abstract:

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD.

Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.

Keywords: Alzheimer's disease, peroxisome proliferator activated receptors, β-amyloid, oxidative stress, neuroinflammation, energy metabolism, PEA, fibrates.

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Article Details

VOLUME: 15
ISSUE: 4
Year: 2018
Page: [345 - 354]
Pages: 10
DOI: 10.2174/1567205014666170505094549
Price: $58

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